Single-photon emission computed tomography (SPECT) has become an important diagnostic tool in nuclear medicine for imaging the heart, brain, liver, bones, and other organs because it is non-invasive and is less expensive than other modalities--for example, positron emission tomography (PET). The use of cone-beam collimators with SPECT has increased the sensitivity for imaging small organs like the brain and heart by taking advantage of the large field-of-view rotating gamma camera to magnify small organs onto a large detector area. The use of cone-beam collimators has demonstrated improved sensitivity and resolution over the use of parallel hole collimators, and has resulted in better detection and sizing of, for example, cardiac lesions with no increase in scanning time. However, with present SPECT systems, which have only single planar orbits, the application of cone-beam tomography to some structures shows slice-to- slice cross-talk. For organs like the brain this system shows image elongation along the axis of rotation near the top of the head in coronal and sagittal views due to insufficient data. To achieve sufficient data it is necessary for the scanning trajectory of the focal point to have at least one point of intersection for any plane passing through the reconstructed region of interest. This may require hardware modifications of present SPECT systems; however, even if sufficient data sampling is available, efficient analytical algorithms are not guaranteed. The proposed research will develop algorithms for reconstructing cone-beam projections with sufficient data sampling. Of special emphasis is the development of algorithms applicable to SPECT systems that can be modified with little or no additional cost to present clinical systems. The overall goal of the project is to develop efficient cone-beam reconstruction algorithms that provide artifact-free three-dimensional SPECT reconstructions for clinical use. The results will have the potential to significantly improve the diagnostic capability of nuclear medicine procedures. Upon completion of the project, software will be developed and tested. The research will develop engineering principles and guidelines for the design of SPECT systems that acquire sufficient data for cone-beam tomography and clinical protocols for acquiring and processing sufficient cone-beam data.